This application is for a supplement to our current program project grant which is concerned with the pathophysiology and treatment of coronary artery disease. The supplement will enable Dr. Connor of Iowa City to come to University of Oregon to continue his research and, in addition, we will develop common research interests. The primary objectives of the research are to understand the physiology and biochemistry of sterols, as related to the development of atherosclerosis in man, and to elucidate nutritional and pharmacologic techniques to treat the abnormalities detected. The metabolic reasons for individuals under the same environment and dietary circumstances having low and high levels of beta-lipoprotein will be investigated with regard to environment and genetic aspects in an attempt to answer these questions: What is the inherited biochemical, and what is the acquired biochemical lesion of sterol metabolism so common in the Western world? More specifically, we seek to understand the intestinal absorption of sterols (cholesterol, cholestanol, plant sterols, seafood sterols); their transport in the plasma; their uptake by tissues such as arteries to produce artherosclerosis, and by other tissues for storage; their interactions; their excretion; and their metabolism under the influence of nutritional factors and drugs. The uptake and metabolism of free and esterified cholesterol from various lipoproteins by cultured human endothelial cells will be studied to ascertain the mechanisms of atherosclerotic plaque formation and regression. There are 17 discrete but interrelated research projects grouped under three broad sections: A. The effects of diet upon the serum lipids and lipoproteins and the sterol balance in man; B. The cholesterol turnover and uptake by the tissues; and C. Disease of lipid metabolism: Pathophysiology and treatment.